Antipsychotic switching versus augmentation among early non-responders to risperidone or olanzapine in acute-phase schizophrenia.

PURPOSE: We examined whether augmentation with olanzapine would be superior to switching to olanzapine among early non-responders (ENRs) to risperidone, and whether augmentation with risperidone would be superior to switching to risperidone among ENRs to olanzapine. We performed a rater-blinded, randomized clinical trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. ENRs to the initial antipsychotic (Clinical Global Impressions-Improvement Scale: ≥ 4 at 2 weeks) were allocated to receive either augmentation with or switching to the other antipsychotic (RIS+OLZ vs. RIS-OLZ; OLZ+RIS vs. OLZ-RIS) RESULTS: Sixty patients who completed 2 weeks of risperidone treatment were divided into 33 early responders (RIS-ER) and 27 ENRs (RIS+OLZ, n=14; RIS-OLZ, n=13). Although time to treatment discontinuation for any cause was significantly shorter in RIS+OLZ group (54.1 days [95% confidence interval, 41.3-67.0]) than in RIS-ER group (68.7 [61.2-76.2]; P=0.050), it was not significantly shorter in RIS-OLZ group (58.5 [43.1-73.9]) than in RIS-ER group (P=0.19). Sixty patients who completed 2 weeks of olanzapine treatment were divided into 36 early responders (OLZ-ER) and 24 ENRs (OLZ+RIS, n=11; OLZ-RIS, n=13). Although time to treatment discontinuation for any cause was significantly shorter in OLZ-RIS group (56.1days [40.7-71.5]) than in OLZ-ER group (74.9 [68.5-81.3]; P=0.008), it was not significantly shorter in OLZ+RIS group (64.6 [49.6-79.6]) than in OLZ-ER group (P=0.20). CONCLUSION: Despite the lack of pharmacokinetic investigation of dose adequacy in this study, it is possible that switching to olanzapine among ENRs to risperidone might have a small advantage over augmentation with olanzapine, while augmentation with risperidone might have a small advantage over switching to risperidone among ENRs to olanzapine. Further research is required before it would be appropriate to modify routine practice in the direction of these findings.

A comparison between augmentation with olanzapine and increased risperidone dose in acute schizophrenia patients showing early non-response to risperidone.

We examined whether augmentation with olanzapine would be superior to increased risperidone dose among acute schizophrenia patients showing early non-response to risperidone. We performed a rater-blinded, randomized controlled trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as Clinical Global Impressions-Improvement Scale score ≤3 following 2 weeks of treatment. Early non-responders were allocated to receive either augmentation with olanzapine (RIS+OLZ group) or increased risperidone dose (RIS+RIS group). The 78 patients who completed 2 weeks of treatment were divided into 52 early responders to risperidone and 26 early non-responders to risperidone (RIS+OLZ group, n=13; RIS+RIS group, n=13). No difference in the achievement of ≥50% improvement in Positive and Negative Syndrome Scale total score was observed between RIS+OLZ and RIS+RIS groups. Although time to treatment discontinuation for any cause was significantly shorter in the RIS+RIS group (6.8 weeks [95% confidence interval, 5.2-8.4]) than in early responders to risperidone (8.6 weeks [7.9-9.3]; P=0.018), there was no significant difference between the RIS+OLZ group (7.9 weeks [6.3-9.5]) and early responders to risperidone. Secondary outcomes justify the inclusion of augmentation arms in additional, larger studies comparing strategies for early non-responders.

Difference in early prediction of antipsychotic non-response between risperidone and olanzapine in the treatment of acute-phase schizophrenia.

PURPOSE: We examined whether early response/non-response to risperidone according to the Clinical Global Impressions-improvement scale (CGI-I) at 2 weeks could predict subsequent response. This prediction was also applied to olanzapine. We then investigated whether early non-responders (ENRs) to risperidone or olanzapine who switched to the other showed significantly greater improvement, compared with those staying on the initial antipsychotic. We performed a rater-blinded, randomized controlled trial in 18 psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as CGI-I ≤ 3 following 2 weeks of treatment. The primary outcome measure was achievement of remission and ≥ 50% improvement in the Positive and Negative Syndrome Scale at 4 weeks. RESULTS: At 4 weeks, 53% of risperidone early responders (ERs) went into remission, whereas only 9% of ENRs staying on risperidone (n=11) did (P=0.016). Similarly, at 4 weeks, 81% of risperidone ERs achieved ≥ 50% response, whereas only 9% of ENRs staying on risperidone achieved ≥ 50% response (P < 0.0001). In contrast, 58% of olanzapine ERs (n=33) went into remission, whereas 38% of ENRs staying on olanzapine (n=8) did at 4 weeks (P=0.44). Similarly, 61% of olanzapine ERs achieved ≥ 50% response, whereas 25% of ENRs staying on olanzapine achieved ≥ 50% response (P=0.12). The negative likelihood ratio for the prediction of ≥ 50% response at 4 weeks by early response status to risperidone at 2 weeks was 0.057. CONCLUSION: In newly admitted patients with acute schizophrenia, non-response to risperidone using CGI-I at 2 weeks can predict subsequent response. It looks like there is significant response to olanzapine that doesn't occur until 4 weeks. Thus, clinicians may want to switch to another drug earlier when risperidone is the first drug, and later when olanzapine is the first drug.